tbuckley/cabot-search huggingface dataset:
Mastectomy and immediate prepectoral versus submuscular breast reconstruction after neoadjuvant chemotherapy: Our early experience.
Authors: Lorenzo Scardina, Francesca Moschella, Stefano Magno, Alejandro Martin Sanchez, Alba Di Leone, Sabatino D'Archi, Antonio Franco, Ersilia Biondi, Beatrice Carnassale, Annalisa Di Micco, Emilio Bria, Riccardo Masetti, Gianluca Franceschini
Journal: Journal of Clinical Oncology (2022)

e12618 Background: Conservative mastectomy with immediate prosthetic breast reconstruction (IPBR) is an oncologically accepted technique that allows to improve aesthetic results and patient quality of life. Traditionally, implants have been placed in a submuscolar (SM) plane beneath the pectoralis major muscle (PMM). Recently, prepectoral (PP) placement of prosthesis is increasingly used in order to avoid morbidities related to manipulation of PMM. The aim of this study was to compare outcomes of SM vs PP IPBR after conservative mastectomy in patients with histologically proven breast cancer treated with neoadjuvant chemotherapy (NAC). Methods: In this retrospective observational study we analyzed two cohorts of patients that underwent mastectomy with IPBR after NAC in our Istitution from January 2018 to December 2021. Conservative mastectomy was performed in 155 of the 400 patients that underwent NAC during the study period. Patients were divided in 2 groups based on the positioning of implants: 60 SM versus 95 PP. Results: The two cohorts were similar for age (mean age 45 and 42 years in the SM and PP group respectively) and follow‐up (32 and 21 months, respectively). Mean operative time was 55 minutes shorter in the PP group (298 and 243 minutes in the SM and PP group). No significant differences were observed in overall major complication rates. Implant loss occurred was observed in 1.6% of patients (1/60) in the SM group and 1,05% of patients (1/95) in PP group. No differences were observed among the two groups in local or regional recurrence. Conclusions: Our preliminary experience, that represents one of the largest series of PP-IPBR after NAC at a single Institution documented in the Literature, seems to confirm that PP - IPBR after NAC is a safe, reliable and effective alternative to traditional SM - IPBR with excellent aesthetic and oncological outcomes; it is easy to perfom, reduces operative time and minimizes complications related to manipolation of PPM. However this promising results need to be confirmed in prospective trials with longer follow-up.
Checkpoint inhibitor accessibility in 15,000+ Indian patients.
Authors: Madala Ravikrishna, George Abraham, Vijay Maruti Patil, Atanu Bhattacharjee, Vanita Noronha, Nandini Sharrel Menon, Amit Joshi, Kumar Prabhash
Journal: Journal of Clinical Oncology (2022)

9012 Background: Access to newer therapies is an issue in low and low middle income countries. Hence we decided to audit our practice in the head and neck and thoracic medical oncology unit from 2015 to 2019 to study the accessibility of checkpoint inhibitors and factors influencing them. Methods: All patients who were registered in the head and neck and thoracic medical oncology unit between 2015-2019 were included in the study. The number of patients who received immunotherapy among them was identified from the prospective database of immunotherapy maintained in the department. We made a list of patients who were eligible for immunotherapy per year and identified how many of them received recommended immunotherapy. The indication for eligibility of immunotherapy was based on published pivotal data and its date of publication of the study online. For nominal and ordinal variable percentage with 95% CI was provided. Factors impacting the accessibility of immunotherapy were identified. Results: A total of 15,674 patients were identified who required immunotherapy; out of them only 444 (2.83%, 95% CI, 2.58-3.1) received it. The distribution of patients eligible as per cancer disease management group and time period is shown in the Table. Among head and neck cancer patients 4.5% (156 out of 3,435) received immunotherapy versus 2.35% (288 out of 12,239) among thoracic cancer patients (p &lt; 0.0001). Among the general category (low socioeconomic), 0.29% (28 out of 9,405) versus 6.6% (416 out of 6,269) among the private category (high socioeconomic) received immunotherapy (p &lt; 0.0001). While 3.7% (361 out of 9,737) among males versus 1.39% (83 out of 5,937) females received immunotherapy (p &lt; 0.0001). There was also a temporal trend seen in the accessibility of immunotherapy (p &lt; 0.0001, Table). Conclusions: The accessibility of immunotherapy is below 3% in India. Patients with head and neck cancers, those with private category and with male gender had higher access to this therapy. There was also a temporal trend observed suggesting increased accessibility over the years. [Table: see text]
Effects of healthcare provider recommendation for genetic testing.
Authors: Emerson Delacroix, Erika Hanson, Sarah Austin, Grant Carr, Kelley M. Kidwell, Elena Martinez Stoffel, Ken Resnicow
Journal: Journal of Clinical Oncology (2022)

10601 Background: This pilot study was conducted to elucidate the barriers and drivers for genetic testing by combining validated measures to inform the content of a clinical trial aimed at increasing uptake of clinically appropriate genetic testing amongst individuals with a personal history of cancer. Previous research shows that the rate of recommendation of genetic testing varies among Healthcare Providers (HCPs) despite national guidelines. Here we evaluate the rate and effect of HCP recommendation on the uptake of clinical cancer genetic testing. Methods: Data for these analyses were obtained from a cross-sectional survey completed by 794 adults (&gt; 18 years) who were diagnosed with cancer in the past 10 years and were seen at an academic medical center within the past two years. Statistical analysis includes logistic regression and crosstabulation with SPSS and R statistical software. Results: Provider recommendation of genetic testing was found to be a very strong indicator of receiving genetic testing across all cancer types (OR = 146.4, p = &lt;.001). HCPs more frequently recommended genetic testing to females (OR = 12.5, p = &lt;.001), younger patients (OR = 1.05, p = &lt;.001). While females are more likely to receive a recommendation, there were no significant differences on genetic testing uptake when a HCP recommended it for any gender. Conclusions: Without the recommendation of their provider, patients were significantly less likely to receive genetic testing that could affect their cancer treatment, surveillance, or family members. More aggressive patient health education is needed in cancer affected patients to decrease knowledge deficits and increase motivation for cancer genetic testing uptake. Education to providers regarding genetic testing recommendation guidelines could increase motivation to refer patients for genetic testing and counseling.
Predicting immune checkpoint inhibitor-related hepatitis using electronic health records of patients.
Authors: Gergely Horváth, Zoltán Kiss, Eszter Csernai, Levente Lippenszky, Pablo Napan-Molina, Michele LeNoue-Newton, Kathleen Mittendorf, David Smith, Ben Ho Park, Jan Wolber, Travis John Osterman
Journal: Journal of Clinical Oncology (2022)

e13564 Background: Immune checkpoint inhibitor (ICI) therapies have shown impressive results in treating oncology patients. However, some patients exhibit immune-related adverse events (irAE-s), one significant irAE is autoimmune hepatitis. Oncologists routinely screen for hepatic toxicity with a complete metabolic panel prior to each ICI administration. Predictive modeling of irAE-s based on patient factors has the potential to help guide treatment selection and monitoring protocols. We have developed a widely usable model based on patient history and routinely collected standard blood panels that can predict whether a patient will experience hepatitis with ICI administration. Methods: We defined irAE hepatitis as any single value of AST, ALT, or alkaline phosphatase three-times the upper limit of normal (ULN) as following ICI treatment. The goal was to determine whether the level of the biomarkers exceed this threshold within certain, pre-defined time-windows, as determined by medical experts. We used feature engineering to compress the time-series of lab panels into single meaningful statistical descriptors, such as mean or maximum of these vectors. The dataset was highly unbalanced with many more negative cases (out of the 3231 patients, depending on the window length used for feature generation, 100-400 positives were found), which warranted the application of synthetic resampling methods. Finally, we trained various ensemble models ( e.g., random forest, gradient boosting), on both the resampled and original dataset, to obtain the final, predictive model for the likelihood of irAE hepatitis. Models were tuned to favor high recall and lower precision (identification of patients for increased monitoring) or moderate recall and moderate precision (maximizing F1-score). Results: We explored several modelling methods, such as KNN, Logistic Regression, Random Forests (RF), Gradient Boosting (GB), and stacking. GB without resampling produced the best model with the moderate recall and precision. To achieve high recall with low precision, we needed to resample the dataset with random majority class under sampling and then use RF (see table below for exact results). Conclusions: In this study, we show contemporary machine learning methods can be used as a screening tool for patients at risk for irAE hepatitis. This method could be used to identify patients who would benefit from additional laboratory monitoring between ICI administrations or guide clinical decisions about therapy cessation in advance of toxicity. Additionally, these methods may be further developed and adapted to improve clinical trial exclusion criteria for patients most likely to develop irAE hepatitis.[Table: see text]
DDEL-06. Drug Delivery to the Pons Using Short-Pulse Focused Ultrasound and Microbubble Exposure for the Treatment of Diffuse Midline Glioma
Authors: Dani Chattenton, Ian Rivens, Zheng Jiang, Diana M Carvalho, Krit Sujarittam, Jessica K R Boult, Simon P Robinson, Chris Jones, Gail ter Haar, James Choi
Journal: Neuro-Oncology (2022)

Abstract Despite advances in understanding diffuse midline glioma (DMG-H3K27), including DIPG, there are still no effective treatments available, and the dismal clinical prognosis remains. This is partly because of tumour spread behind an intact blood brain barrier (BBB), preventing drug delivery and the reason for many drugs failing in the clinic. The use of focused ultrasound and intravenous microbubbles enables temporary increases in BBB permeability, allowing drugs to enter the targeted brain region. Building on recent research demonstrating that short pulses (&amp;lt;5 µs) of ultrasound can deliver drugs safely and uniformly to the hippocampus, we evaluated whether a similar result was achievable in the pons of mice. Mice were exposed to ultrasound (peak-negative pressure: 0.4 MPa, pulse length: 5 cycles, centre frequency 1 MHz) emitted in bursts of 38 pulses. During exposure mice received an intravenous injection of SonoVue(R) microbubbles and a fluorescently-tagged tracer (dextran, 3 kDa), acting as a drug mimic. Dextran was successfully delivered to the pons of non-tumour-bearing mice assessed by fluorescence microscopy immediately post-treatment. Dextran delivery was repeatable and confined to the targeted pons region with a homogenous distribution, typical of short pulse ultrasound, and important for treating DMG to ensure all tumour cells receive an equal drug dose. No damage to the brain was observed after H&amp;E staining. Panobinostat has shown promise in vitro but tolerated doses have not shown therapeutic benefit in vivo as it does not cross the BBB. The in vitro toxicity of panobinostat was confirmed in a Nestin-Tv-a/p53fl/fl, RCAS-ACVR1R206H + RCAS-H3.1K27M murine cell line, with a GI50 of 15.56 nM. The ability of focused ultrasound to deliver panobinostat across the BBB to these tumours grown orthotopically will be assessed. Overall, we hope to develop a drug delivery system, that enables therapeutics to cross the BBB, expanding treatment options for DMG.
The prognostic impact of immune-related adverse events in real-world patients with metastatic melanoma treated with single-agent and combination immune checkpoint blockade.
Authors: Alexander Watson, Siddhartha Goutam, Igor Stukalin, Benjamin Ewanchuk, Michael Sander, Daniel E. Meyers, Aliyah Pabani, Winson Y. Cheung, Daniel Yick Chin Heng, Tina Cheng, Jose Gerard Monzon, Vishal Navani
Journal: Journal of Clinical Oncology (2022)

9542 Background: Immune checkpoint blockade (ICB) has revolutionized the treatment of metastatic melanoma (MM). Immune-related Adverse Events (irAEs) associated with ICB have been shown to correlate positively with survival outcomes across solid tumours. In MM, conclusions on the impact of irAE severity have been conflicting, and combination ICB therapy experience is limited to smaller cohorts. We sought to clarify these relationships using the Alberta Immunotherapy Database (AID). Methods: The AID provides a multi-centre, province-wide observational cohort comprising consecutive patients treated with ICB. We included adult patients with MM, treated with ICB (single agent nivolumab or pembrolizumab, or combination ipilimumab and nivolumab) at any line of therapy, agnostic to site of origin, from August 2013 to May 2020, with analysis in December 2021. The primary endpoint of interest was the identification of a relationship between development of irAEs and subsequent overall survival (OS, defined from time of ICB initiation). To minimize immortal time bias from poor prognosis patients who may have died prior to the development of irAEs, patients who died before 12 weeks were excluded from OS and time-to-next-treatment (TTNT) analysis. Adjusted Cox regression analyses were performed to determine the association of variables with OS. Results: Of 492 MM patients receiving ICB, 124 received combination ICB, 198 developed an irAE and 67 required hospitalization for an irAE. irAEs were more common in patients &lt; 50 years old (p = 0.02), with ECOG 0 (p &lt; 0.001) and normal albumin (p = 0.002). Median time to irAE development (2.6 months) and frequency of individual irAEs were consistent with the published literature. In the overall population, patients who experienced an irAE had longer median OS (56.3 vs 18.5mo, p &lt; 0.0001), and TTNT (49.6 vs 12.9mo, p &lt; 0.0001). This remained consistent in combination ICB-treated patients (median OS 56.3 vs 19mo, p &lt; 0.0001). Patients hospitalized for an irAE had improved OS and TTNT over patients requiring only outpatient treatment (median OS NR vs 27.9mo, p = 0.0039), while ICB re-challenge after an irAE also improved OS (56.3 vs 31.5mo, p = 0.0093). Development of an irAE retained independent association with OS after adjusted multivariable regression (HR 0.376, p &lt; 0.001). Conclusions: These data support the association of irAEs and improved survival outcomes in MM, including those patients treated with combination ICB. Among patients with irAE, hospitalization for irAE, and ICB re-challenge post-irAE, were further associated with improved outcomes.
Development of novel stratification systems to guide treatment for NMIBC based on results from SIPRES study (multi-institutional prospective study)
Authors: M. Uemura, A. Nagahara, T. Ujike, R. Tanaka, W. Nakata, S. Kamido, T. Takada, Y. Yamanaka, Y. Miyagawa, G. Tanigawa, H. Arai, Y. Sekii, K. Fujita, J.-I. Ikeda, A. Miyake, N. Nonomura
Journal: European Urology (2022)
Nanosensitizers for sonodynamic therapy for glioblastoma multiforme: current progress and future perspectives
Authors: Qing-Long Guo, Xing-Liang Dai, Meng-Yuan Yin, Hong-Wei Cheng, Hai-Sheng Qian, Hua Wang, Dao-Ming Zhu, Xian-Wen Wang
Journal: Military Medical Research (2022)

Abstract Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood–brain barrier (BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy (SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research.
Phase I trial of the RAF/MEK clamp VS-6766 in combination with everolimus using an intermittent schedule with expansion in NSCLC across multiple <i>KRAS </i>variants.
Authors: Anna Rachel Minchom, Vicky Sanchez Perez, Cienne Morton, Thubeena Manickavasagar, George Nintos, Julia Elizabeth Lai-Kwon, Christina Guo, Nina Tunariu, Tom Parker, Toby Prout, Mona Parmar, Alison Joanne Turner, Laura Finneran, Emma Hall, Jonathan A. Pachter, Louis J. Denis, James F. Spicer, Udai Banerji
Journal: Journal of Clinical Oncology (2022)

9018 Background: VS-6766 is a small molecule RAF/MEK clamp that results in the reduction of p-MEK and p-ERK. Preclinical data show synergy of VS-6766 with the mTOR inhibitor everolimus across a panel of KRAS mutated (mt) NSCLC cell lines. This clinical trial evaluated the safety and efficacy of a novel intermittent regimen of VS-6766 and everolimus with an expansion in KRAS mt NSCLC (NCT02407509). Methods: The trial used a 3+3 dose escalation design with an intermittent once a week schedule A, and if tolerated, twice a week schedule B (Mon-Thu or Tue-Fri) for both drugs on a 3 weeks on/1 week off, 28 day cycle. Patients with RAS or RAF mt cancers were eligible for the dose escalation cohort, and 20 patients with KRAS mt NSCLC will be treated in the dose expansion cohort. Toxicity was evaluated by NCI CTC V4 and efficacy was evaluated using RECIST 1.1. Results: A total of 28 patients have been treated; median age 60 yrs (range 36-78), and median lines of previous treatment 3 (range 0-7). Sixteen patients have been treated in the dose escalation (3 in schedule A and 13 in the schedule B). The doses of 4 mg of VS-6766 and 5 mg everolimus (once weekly) were tolerated with no dose limiting toxicities (DLTs) and the dose intensity escalated to schedule B (twice weekly). At 4 mg VS-6766 twice weekly, DLTs were observed in two out of six patients and included grade 4 CPK elevation and grade 3 rash. Thus, the dose in schedule B (twice weekly) was de-escalated to 3.2 mg VS-6766 and the dose of everolimus was kept at 5 mg. No DLTs were reported in 6 patients and thus this was declared as the recommended phase 2 dose (RP2D). At the RP2D, the grade 3-4 drug related AE were rash (18%) and pruritus (7%). In the dose escalation cohorts, 3 partial responses (PRs) were reported (2 KRAS G12D low grade serous ovarian cancer and 1 NRAS Q61K mt thyroid cancer). In the KRAS mt NSCLC expansion cohort, 10 patients are evaluable for efficacy and 2 confirmed responses were reported ( KRAS mutations G12V and G13A) with an objective response rate (ORR) 20% to date. The disease control rate (PR + SD) at the first scheduled evaluation was 90%. The median progression free survival (PFS) in the KRAS mt NSCLC cohort is 6.35 months (95% CI 3.52 – not reached). Updated ORR and PFS data will be presented. Conclusions: A tolerable intermittent dosing schedule targeting both the MAPK and PI3K pathways has been established. The combination of VS-6766 with everolimus has shown activity in patients with a variety of KRAS mutation variants including responses in KRAS mt NSCLC.
SWK-05. Clinical social work in pediatric neuro-oncology – A research project on the social dimension using social diagnostics
Authors: Kerstin Krottendorfer, Verena Rosenmayr, Liesa Josephine Weiler-Wichtl, Thomas Pletschko, Andreas Peyrl, Ulrike Leiss
Journal: Neuro-Oncology (2022)

Abstract PURPOSE: A neuro-oncological disease of a child represents a high psychosocial burden for the whole family (Wiener, Kazek et al. 2015). A biopsychosocial and family-oriented approach for the treatment of children and their families focusing on medical, psychological and social care is significant in the course of the disease. Studies show that existential problems or lack of social support are risk factors. Therefore, this research investigates the impact of a pediatric neuro-oncological disease on the social dimension using a standardized social assessment. RESEARCH DESIGN: The project is based on a retrospective cross-sectional study (04/2015-12/2021) including consecutive patients with high- or low-grade gliomas at the Medical University of Vienna - Department of Pediatrics (n= 160). By using a specialized and standardized social diagnostic tool (DISAPO) starting at the onset of disease, the clinical social worker surveys the social situation (social network, work situation, financial and housing situation, legal status, insurance status, etc.) with the parents. Based on the assessed social situation the clinical social work interventions (CSWI) are recorded throughout the child′s treatment. The results are statistically evaluated including medical data. RESULTS: The results of the DISAPO show that in the course of the disease all families need CSWI in one or more areas of the social dimension: disease-related interventions: 100%, work intervention: 80,6% (n=129), living situation: 43,8% (n=70), social support: 39,4% (n=63), socioeconomic interventions: 19,4% (n=31), residence law aspects: 18,8% (n=30). CONCLUSION: These results emphasize that in case of a pediatric neuro-oncological disease the social dimension is always affected and comprehensive CSWI are highly needed. For a holistic care of the patients and their families a biopsychosocial standard-of-care including all professions is indispensable. In addition, a standardized approach for assessment and intervention showed that needs could be assessed more adequately and interventions more targeted.